摘要
磷酸二酯酶(PDE)是一个多基因家族,通过水解环磷酸腺苷(cAMP)和环磷酸鸟苷(cGMP),调节其细胞内浓度发挥生物学功能。研究表明,cAMP和cGMP信号通路与肿瘤细胞的增殖、凋亡、转移等密切相关,因此,靶向调控PDE即可影响肿瘤发生发展。PDE抑制剂通过靶向调节结构域抑制酶的活性,导致cAMP和cGMP无法水解,进而激活P38丝裂原活化蛋白激酶,cAMP/蛋白激酶A/cAMP反应原件结合蛋白和蛋白激酶G等信号通路,抑制细胞周期,凋亡和转移。此外,PDE在部分肿瘤中过表达,有望成为肿瘤分子标记物,是开发抗肿瘤药物的理想靶点。本文对PDE的结构和功能,各亚型及其抑制剂在抗肿瘤中的作用研究进展进行归纳,同时对PDE调控肿瘤发生发展的分子机制进行了分析。
As a multigene family, phosphodiesterases(PDEs) catalyze hydrolysis of cyclic adensine monophosphate(cAMP) and cyclic guanos monophosphate(cGMP), and regulate their intracellular concentrations and their biological effects. A number of studies have showed that c AMP/cGMP signaling pathways are closely related to tumor proliferation, apoptosis and metastasis, which is why targeting PDEs has significant effects on cancer. PDE inhibitors inhibit cell cycle, apoptosis and metastasis by targeting structural domains that inhibit enzyme activity, causing the failure of the cAMP and cGMP to hydrolyze, which activates such signaling pathways as P38 mitogen-activated protein kinase, cAMP/protein kinase A/cAMP-response element binding protein and protein kinases G. In addition, PDE is overexpressed in some tumors and is expected to be a molecular marker for tumors, itself an ideal target for the development of anti-tumor drugs. This paper summarizes the structure and function of PDE, the research progress in each isoform and its inhibitors in tumors, and analyzes the molecular mechanism by which PDE regulates tumor development.
作者
张作艳
李杨玲
周旋
林珠
朱素燕
徐萍
张翀
ZHANG Zuo-yan;LI Yang-lin;ZHOU Xuan;LIN Zhu;ZHU Su-yan;XU Ping;ZHANG Chong(Department of Pharmacy,Ningbo First Hospital,Ningbo 315000,China;Department of Clinical Pharmacy,Affiliated Hangzhou First People′s Hospital,Zhejiang University School of Medicine,Hangzhou 310006,China;School of Medicine,Zhejiang University City College,Hangzhou 310015,China)
出处
《中国药理学与毒理学杂志》
CAS
北大核心
2022年第11期862-871,共10页
Chinese Journal of Pharmacology and Toxicology
基金
国家自然科学基金(81702887)
浙江省自然科学基金华东医药联合基金(LHDMY22H160001)
宁波市自然科学基金(2022J206)。
